In this episode, we’re joined by Dr. David Perlmutter — neurologist, bestselling author of Grain Brain and Drop Acid, and one of the longest-standing voices in preventive neurology. His new book, Brain Defenders (August 2026), pulls together four decades of work into a single mechanism: the brain’s own immune cells, called microglia, and how our daily choices determine whether they protect us or turn destructive.
Topics and questions covered:
How Dr. Perlmutter’s curiosity about insulin resistance and cognitive decline led to Grain Brain and the broader mission of preventive neurology
Microglia: what they are, what they do during development (synaptic pruning), and what happens when the same process reactivates later in life
How complement proteins tag synapses with “eat me signals” — and why inflammation drives the tagging
Is the tide changing on dementia prevention?
The potential impact of declining cognitive stimulation on microglial activation and synaptic pruning
The evolutionary story of uric acid: why we lost uricase, how fructose signals “winter is coming,” and what happens when that signal never stops
The alarming impact of ultra-processed foods on dementia risk
His number one recommendation for brain health (it’s not a supplement)
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